Cell therapy manufacturing of primary T cells often results in heterogeneous cell populations within a final product, with many cells lacking desired receptor expression or exhausted and other dysfunctional phenotypes. Here, we design a novel cell-intrinsic strategy to genetically reprogram primary human T cells to autonomously detect and eliminate dysfunctional cells. This integrated detection and […]
Early cell autonomous and niche-mediated alveolar epithelial response to influenza infection in primary lung organoids
Influenza A virus (IAV) infection is a significant cause of morbidity and mortality for patients worldwide. Alveolar type 2 (AT2) cells are the preferential target of IAV as part of the pathogenesis of viral pneumonia and acute respiratory distress syndrome (ARDS). Early IAV infection of alveolar cells has been challenging to model both in vitro […]
Preoptic activation induces a torpor-like hypothermic and hypometabolic state that is cerebroprotective
Therapeutic hypothermia for stroke has been limited by shivering, increased metabolic demand, and poor patient tolerance. Engaging endogenous thermoregulatory circuits to lower body temperature may overcome these limitations and modulate metabolism, offering an integrated approach to cerebroprotection. Here, we show that chemogenetic activation of neurons in the preoptic area (POA) elicits a torpor-like state in […]
Aromatic residues in mobile regions distal to the active site support the closed conformation of E. coli DXPS
The essential bacterial enzyme 1-deoxy-D-xylulose 5-phosphate synthase (DXPS) is absent in humans, making the enzyme an attractive antimicrobial target. Its product DXP sits at a metabolic branchpoint between the biosynthesis of pyridoxal phosphate (PLP), thiamin diphosphate (ThDP), and isoprenoids. DXP is formed via decarboxylation of pyruvate and subsequent carboligation with D-glyceraldehyde-3-phosphate (D-GAP) in a ThDP-dependent […]
Dorsal forerunner cells transmit epiboly forces to extend the zebrafish notochord
Convergence and extension (C&E) cell movements promote anteroposterior axis extension and narrow both neuroectodermal and mesodermal tissues during gastrulation. Mediolateral cell intercalation is largely responsible for this morphogenetic process in vertebrates, but evidence suggests that additional cell-extrinsic forces generated by surrounding tissues contribute to the shaping of many structures. In zebrafish, for example, mechanical forces […]
Cln3 can work independently of Whi5 on the cell size for Start in yeast
In yeast, cells commit to division at Start in G1 phase. The critical cell size for Start is regulated in part by the size-control genes CLN3 and WHI5. Cln3 is a G1 cyclin that activates Start by activating the Cdc28 cyclin dependent kinase. Null cln3 mutants have large cells, because they lack an activator, while […]
Distinct Roles of Surface Nanostructure and Polymer Degradation in Fibroblast Response to Device Design
Fibrotic encapsulation of implanted biomedical devices represents the highest cause of device failure across numerous fields, including orthopedics, breast implants and neural electrodes. While most research has focused on the immune system for driving the foreign body response to devices, fibroblasts are emerging as another key regulator of tissue response. In the present study, we […]
Modulating inter-mitochondrial contacts to increase membrane potential for mitigating blue light damage
Mitochondrial membrane potential (MMP) is essential for mitochondrial functions, yet current methods for modulating MMP lack precise spatial and temporal control. Here, we present an optogenetic system that enables reversible formation of inter-mitochondrial contacts (mito-contacts) with high spatiotemporal precision. Blue light stimulation induces rapid formation of mito-contacts, which fully dissipate upon cessation of illumination. These […]
Encoded cell-material interactions to reroute cytokine signaling for regenerative medicine
Regenerative engineering harnesses materials science and stem cell biology to develop strategies to repair damaged and diseased tissue. Despite advances in designer materials, few techniques effectively provide auto-regulated feedback mechanisms that govern how cells sense and respond to discrete microenvironmental changes. Here, we demonstrate that the artificial, juxtacrine-like receptor synthetic Notch (synNotch) can be activated […]
Failure of DNA repair leads to the tumorigenic transformation of a regenerating blastema in Drosophila imaginal discs
We present a Drosophila model demonstrating that repeated cycles of tissue regeneration following localized apoptosis can induce tumorigenesis in the absence of oncogene activation or tumor suppressor loss. Chronic regenerative stress leads to epithelial disorganization, loss of cell polarity, immune cell infiltration, DNA damage, centrosomal defects, and aneuploidy–classical hallmarks of cancer. A subset of ”walking […]